摘要:

Heart rate (HR) has been widely studied as a measure of an individual's response to painful stimuli. It remains unclear whether changes in mean HR or the variability of HR are specifically related to the noxious stimulus (i.e.pain). Neither is it well understood how such changes reflect underlying neurologic control mechanisms that produce these responses, or how these mechanisms change during the first year of life. To study the changes in cardiac autonomic modulation that occur with acute pain and with age during early infancy, the relationship between respiratory activity and short-term variations of HR (i.e.respiratory sinus arrhythmia) was quantified in a longitudinal study of term born healthy infants who underwent a finger lance blood collection at 4 months of age (n= 24) and again at 8 months of age (n= 20). Quantitative respiratory activity and HR were obtained during baseline, lance, and recovery periods. Time and frequency domain analyses from 2.2-min epochs of data yielded mean values, spectral measures of low (0.04-0.15 Hz) and high (0.15-0.80 Hz) frequency power (LF and HF), and the LF/HF ratio. To determine sympathetic and parasympathetic cardiac activity, the transfer relation between respiration and HR was used.At both 4 and 8 months, mean HR increased significantly with the noxious event (p> 0.01). There were age-related differences in the pattern of LF, HF, and LF/HF ratio changes. Although these parameters all decreased (p> 0.01) at 4 months, LF and LF/HF increased at 8 months and at 8 months HF remained stable in response to the noxious stimulus. Transfer gain changes with the lance demonstrated a change from predominant vagal baseline to a sympathetic condition at both ages. The primary finding of this study is that a response to an acute noxious stimulus appears to produce an increase in respiratory-related sympathetic HR control and a significant decrease in respiratory-related parasympathetic control at both 4 and 8 months. Furthermore, with increasing age, the sympathetic and parasympathetic changes appear to be less intense, but more sustained.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Clinical observation suggest that sepsis may enhance the risk of kernicterus. This study investigated the combined effects of bilirubin, endotoxin, and tumor necrosis factor-α (TNF-α), which simulate sepsis in a jaundiced mouse fibroblast cell line. The horseradish peroxidase oxidation method was applied for bilirubin-albumin titration studies to test the effect of endotoxin and TNF-α on bilirubin-albumin binding. A modified 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide method was used to study cytotoxicity. Bilirubin caused cytotoxicity in a dose-dependent manner in the cultured mouse fibroblasts. Such an effect was significantly amplified by TNF-α and endotoxin. TNF-α and endotoxin had no effect on the bilirubin-albumin titration curves. Our results have shown that TNF-α and endotoxin increase the cytotoxicity of bilirubin. These findings provide supportive evidence that sepsis would increase the risk of tissue damage by bilirubin.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Almitrine is a piperazine derivative known to stimulate breathing in the adult but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147 d) we confirmed this finding, but found that almitrine (4 mg/kg, i.v. or intra-arterial) had a biphasic effect, briefly stimulating and then suppressing breathing movements for at least 3 h. In 2- to 3-d-old (n= 4) and 7- to 14-d-old (n= 4) lambs almitrine increased both tidal volume and breath frequency, increased arterial partial pressure of oxygen and pH, and decreased partial pressure of carbon dioxide. The changes of tidal volume, partial pressure of oxygen and partial pressure of carbon dioxide were less in the 2- to 3-d-old compared with the 7- to 14-d-old lambs. The distribution of the nuclear phosphoprotein FOS, a marker of neuronal activation was examined in fetal and newborn brains. FOS protein was increased in cardiorespiratory areas of the medulla and pons, in the periaqueductal region of the midbrain, and in the supraoptic and paraventricular regions of the hypothalamus. In the pons, FOS protein was increased in the medial parabrachial and subcoeruleus nuclei in the fetuses but not in the 2- to 3- or 7- to 14-d-old lambs. These observations are similar to those reported for hypoxia, and consistent with the hypothesis that both almitrine and hypoxia inhibit fetal breathing movements by an action on a select group of pontine neurons. Whether these neurons respond directly to these stimuli or receive input from the other centers is yet to be elucidated. The mechanisms that change the almitrine (and hypoxia) response from inhibition to excitation at birth have not been identified, but may be important in preventing apnea in the newborn.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Osteoporosis in adult life is associated with a significant morbidity and may be predisposed to by osteopenia and failure to reach peak bone mass in childhood. Children treated for acute lymphoblastic leukemia (ALL) may be at risk of osteopenia as a result of previous therapy or as a consequence of the disease process itself. Dual energy x-ray absorptiometry measurements of bone mineral content (BMC) for the whole body and at the lumbar spine and hip were taken in 35 (14 male) long-term survivors of ALL and compared with results in 20 (10 male) survivors of other malignancies and 31 (17 male) healthy sibling controls. The measured BMC was expressed as a percentage of a predicted value derived from the control group and based on the variables that had influence upon it. BMC (%) was reduced at the spine in the ALL group compared with controls [92.4 (8.0)%versus100.4 (9.7)%, respectively;p< 0.005] and at the hip compared with both other malignancies and controls [89.0 (11.5)%versus96.1 (11.7)% and 100.4 (9.2)%, respectively;p< 0.0005]. Increasing length of time off therapy was associated with a significant increase in %BMC at both the spine and the hip. For the spine, this association was significantly different between the ALL group and other malignancies, suggesting that any gain in %BMC after therapy was slower in children treated for ALL. Both exercise capacity and levels of physical activity were correlated with %BMC at the hip (r= 0.44,p< 0.001 andr= 0.29,p< 0.01, respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine and cisplatin was associated with a reduction at the hip. In conclusion, children treated for ALL are osteopenic. The mechanism is probably multifactorial but is partially related to previous chemotherapy, limited exercise capacity, and relative physical inactivity.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Accumulated clinical evidence suggests that alveolar rhabdomyosarcoma (ARMS) is more aggressive than embryonal rhabdomyosarcoma (ERMS). Here, we study six childhood rhabdomyosarcoma cell lines, three ERMS and three ARMS. We have assayed the ability of the tumor cells to grow in culture and in nude mice as well as their propensity for pulmonary metastasis formation by tail vein injection. We also compared levels of c- and N-myc oncogene expression and DNA copy number. We find no correlation of histologic tumor type (i.e.ERMSversusARMS) with growth rate in culture, but we do find suggestive correlations of histologic type with tumorigenicity (mean tumor diameter in millimeters at 6 wk: ARMS 30, ERMS 10;p1= 0.1) and metastasis formation (ARMS 12, ERMS 0;p1= 0.1). These properties also correlate with uniform greater overexpression of c-myc in ARMS (mean 39.3-fold, range 16-83) compared with ERMS (mean 5.3, range 4-8) (p1= 0.05, control fibroblasts = 1). Although c-myc was often amplifiedin vitro(four of six lines), there was no correlation with histologic type (2/3 ARMS, 2/3 ERMS). These data on rhabdomyosarcoma cell lines derived from verified ERMS and ARMS tumors support the impression from previous clinicopathologic observations that ARMS is a more malignant form of rhabdomyosarcoma than ERMS.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Transcranial magnetic stimulation (TMS) has been used to describe cortical plasticity after unilateral cerebral lesions. The objective of this study was to find out whether cortical plasticity occurs after bilateral cerebral lesions. We investigated central motor reorganization for the arm and leg muscles in cerebral palsy (CP) patients with bilateral cerebral lesions using TMS. Seventeen patients (12 with spastic diplegia, 1 with spastic hemiplegia, and 4 with athetoid CP) and 10 normal subjects, were studied. On CT/MRI, bilateral periventricular leukomalacia was observed in all spastic patients with preterm birth. In two normal subjects, motor responses were induced in the ipsilateral tibialis anterior, but no responses were induced in any normal subject in the ipsilateral abductor pollicis brevis (APB) or biceps brachii (BB). Ipsilateral responses were more common among CP patients, especially in TMS of the less damaged hemisphere in patients with marked asymmetries in brain damage: in 3 abductor pollicis brevis, in 6 BBs, and in 15 tibialis anteriors. The cortical mapping of the sites of highest excitability demonstrated that the abductor pollicis brevis and BB sites in CP patients were nearly identical to those of the normal subjects. In patients with spastic CP born prematurely, a significant lateral shift was found for the excitability sites for the tibialis anterior. No similar lateral shift was observed in the other CP patients. These findings suggest that ipsilateral motor pathways are reinforced in both spastic and athetoid CP patients, and that a lateral shift of the motor cortical area for the leg muscle may occur in spastic CP patients with preterm birth.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Nitric oxide plays a major role in vascular tone control. Increased blood levels of bradykinin (BK), which stimulates nitric oxide biosynthesis, occur at birth. BK effects on ductus arteriosus (DA) tone were investigated in fetal rabbit under fetal (2.5% O2"low PO2") and neonatal (30% O2"high PO2") conditions usingin vitroisometric tension studies. Intact and endothelium-denuded DA, contracted with norepinephrine (ED75-90), showed a biphasic response to BK, with relaxation at 10-9to 10-7M BK and contraction at 10-6to 10-5M BK. BK (10-6to 10-5M) contracted intact DA from baseline tension, with greater contraction under high PO2. The B2-receptor antagonist d-Arg-[Hyp3,Thi5,d-Tic7,Oic8]-BK (Hoe-140, 10-7M) abolished relaxation, but not contraction, to BK in intact and denuded DA. The B1-receptor antagonist des-Arg9-[Leu8]-BK (10-7M) reduced BK-induced contraction but not relaxation in intact DA only. Nitric oxide synthase inhibitors,Nω-nitro-L-arginine methyl ester (10-4M) andNω-monomethyl-L-arginine (10-4M) partially inhibited relaxation to BK in intact DA, with L-arginine (3 × 10-4M) reversingNω-monomethyl-L-arginine inhibition. Nω-nitro-L-arginine methyl ester (10-4M) caused a small but significant inhibition of relaxation to BK in denuded DA. Indomethacin (2.8 × 10-6M), a cyclooxygenase inhibitor, abolished relaxation but not contraction to BK in intact and denuded DA. BK-induced relaxation of the DA acts through B2-receptors, releasing both nitric oxide and prostaglandins, whereas endothelial B1-receptors may mediate contraction. BK action on isolated DA changes from relaxation to contraction as its concentration increases, with greater contraction at neonatal PO2. Thus increased BK levels at birth may aid functional closure of the DA.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

To determine whether acute pulmonary hypertensionin uteroalters fetal pulmonary vascular reactivity, we compared pulmonary vasodilation with an endothelium-dependent agonist, acetylcholine, with that of an endothelium-independent agonist, 8-bromo-guanosine 3′,5′-cylic monophosphate. Acute pulmonary hypertension was produced in chronically prepared, late-gestation fetal lambs by 3 repeated 30-minute partial occlusions of the ductus arteriosus (DA). The first DA compression increased LPA blood flow from 80 ± 10 to 180 ± 21 mL/min (p< 0.01) and decreased pulmonary vascular resistance. In contrast, LPA blood flow did not change and pulmonary vascular resistance increased by 25% during the third period of DA compression. Pulmonary vasodilation during acetylcholine infusion after serial DA compressions was decreased in comparison with the acetylcholine-induced vasodilator response achieved during the baseline period (fall in pulmonary vascular resistance = -49 ± 7% (baseline)versus-25 ± 5% after repeated DA compressions;p< 0.05). In contrast, the vasodilator response to 8-bromo-guanosine 3′,5′-cylic monophosphate remained intact. To determine whether decreased nitric oxide (NO) production may contribute to altered vasoreactivity after acute pulmonary hypertension, repeated DA compressions were performed after treatment with a nonspecific NO synthase inhibitor (nitro-arginine). NO synthase inhibition blocked the pulmonary vasodilation during the first DA compression period, and repeated DA compressions after NO synthase inhibition did not further alter the hemodynamic response to DA compression. These findings support the hypothesis that brief hypertension due to DA compression impairs endothelium-dependent pulmonary vasodilation in the fetus, and that this may be due to decreased NO production.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The aims of this study were1) to compare the effects of lowversushigh doses of indomethacin on cerebral blood flow (CBF) responses to hypercapnia and2) to investigate the effects of low-dose indomethacin on the cerebral vasculature during resting conditions and during vasodilator stimuli. In the first experiment, 27 piglets were randomized into three groups to receive 5 mg/kg indomethacin, 0.2 mg/kg indomethacin, or normal saline. Ninety minutes later, CBF was measured by radioactive microspheres at baseline, during hypercapnia [PaCO2≥ 70 mm Hg (≥9.3 kPa)] and normocapnia. Total CBF was comparable among the three groups at baseline. CBF increased during hypercapnia in all groups, but the hyperemic response was significantly attenuated in the high-dose indomethacin group compared with the saline group but not in the group treated with 0.2 mg/kg. CBF returned toward baseline during normocapnia in all piglets. In the second experiment, a closed cranial window was implanted over the parietal cortex of nine piglets. Cerebrovascular responses to hypercapnia and topical application of isoproterenol (10-7and 10-6M) and histamine (10-6and 10-5M) were investigated before and after administration of 0.2 mg/kg indomethacin. Within 10 min of indomethacin administration, pial arteriolar diameters decreased from 72 ± 8 to 58 ± 6 µm (p< 0.05), and 6-keto-PGF1αconcentration decreased from 1440 ± 250 to 570 ± 30 pg/mL (p< 0.05). Two hours (138 ± 21 min) later, pial arteriolar diameters had returned toward baseline values (65 ± 5 µm), whereas 6-keto-PGF1αvalues remained considerably lower than preindomethacin values (530 ± 30 pg/mL). Cerebrovascular responses to dilator stimuli were preserved after 0.2 mg/kg indomethacin. We conclude that 0.2 mg/kg indomethacin does not markedly affect the cerebral hyperemic responses to hypercapnia in contrast with a very prominent inhibition by 5 mg/kg indomethacin. Also, although indomethacin at a low dose constricts pial arterioles transiently and attenuates cerebral prostanoid production, it does not inhibit the pial arteriolar responsiveness to prostanoid-associated dilator stimuli. This observation may be due to the permissive role that prostacyclin plays in cerebral vasodilatory responses to some vasogenic stimuli such as hypercapnia and histamine.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Intravascular and intraalveolar fibrin depositions in preterm infants with severe respiratory distress syndrome (RDS) have been attributed to activation of clotting. We questioned whether in the face of activated clotting, fibrinolysis is sufficient in these infants. We found, in infants with severe RDS within 6 to 12 h of birth, increased median thrombin-antithrombin III complex formation (11.1versus1.3 ng/mL in the group with mild-to-moderate RDS,p< 0.001), indicating activation of clotting. Simultaneously, we found increased tissue-type plasminogen activator antigen (t-PA) release in plasma of these infants represented by increased median t-PA plasma concentrations (8.3versus2.5 ng/mL in the group with mild-to-moderate RDS,p< 0.01). This increased t-PA release was not accompanied with more plasminogen and antiplasmin consumption and with more fibrin and fibrinogen degradation than in the infants with mild-to-moderate RDS because plasma plasminogen and antiplasmin activity and total fibrin and fibrinogen degradation product concentrations were similar in both groups. We have found that activated clotting and t-PA plasma concentrations are positively correlated with arterial-to-alveolar oxygen tension ratio and ventilator efficiency index values. Plasminogen and antiplasmin activity, and total fibrin and fibrinogen degradation product concentrations were not correlated with these continuous measures of RDS severity. In neonatal RDS, clotting activity contributes to disease severity. Insufficient fibrinolysis likely facilitates the deleterious effects of activated clotting.

ISSN:0031-3998    

出版商:OVID    

年代:1999

数据来源: OVID